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Juan Ding, Yang Liu, David A Sullivan; Effects of insulin and high glucose on human meibomian gland epithelial cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2503.
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© ARVO (1962-2015); The Authors (2016-present)
Type II diabetes is a risk factor for meibomian gland dysfunction (MGD). We hypothesize that this diabetic impact is due, at least in part, to the direct effects of insulin resistance and hyperglycemia on human meibomian gland epithelial cells (HMGECs). To begin to test this hypothesis, we examined whether insulin and high glucose influence immortalized (I) HMGECs. More specifically, we evaluated whether insulin promotes cell proliferation, differentiation and AKT signaling, in a manner similar to that of insulin-like growth factor-1 (IGF-1). We also determined whether high glucose is toxic to IHMGECs, and affects signaling molecules such as insulin receptor (IR), IGF-1R, AKT and ERK, as well as the lipogenesis regulator sterol-regulatory element binding protein (SREBP)-1.
IHMGECs were cultured in serum-containing medium and treated with insulin, IGF-1, IGF-1R blocking antibody, glucose or mannitol for varying time periods. Specific proteins were detected by Western blots, cell proliferation was evaluated by manual cell counting and lipids were assessed with LipidTOX staining and high performance thin layer chromatography.
We found a dose-dependent increase in p-AKT after insulin treatment. However, this signaling occurred at supra-physiological levels of insulin and appeared to be mediated via IGF-1R. Antibody blocking of the IGF-1R diminished the p-AKT signaling induced by insulin. Insulin stimulated cell proliferation and increased the accumulation of neutral lipids, specifically, triglycerides, in IHMGECs. High glucose induced a progressive cell loss, which was accompanied by significantly reduced levels of p-AKT, IGF-1R and SREBP-1. High glucose had no effect on IR or ERK signaling.
Our data show that insulin activates p-AKT via IGF-1R in IHMGECs, and promotes their proliferation and neutral lipid accumulation. Our data also demonstrate that high glucose is toxic to IHMGECs, and decreases the cellular content of p-AKT, IGF-1R and SREBP-1. These results support our hypothesis that insulin resistance and hyperglycemia have a negative effect on HMGECs and may help explain why type II diabetes is a risk factor for MGD.
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